Requirement of the nicotinic acetylcholine receptor β2 subunit for the anatomical and functional development of the visual system

In the mammalian visual system the formation of eye-specific layers at the thalamic level depends on retinal waves of spontaneous activity, which rely on nicotinic acetylcholine receptor activation. We found that in mutant mice lacking the β2 subunit of the neuronal nicotinic receptor, but not in mice lacking the α4 subunit, retinofugal projections do not segregate into eye-specific areas, both in the dorso-lateral geniculate nucleus and in the superior colliculus. Moreover, β2−/− mice show an expansion of the binocular subfield of the primary visual cortex and a decrease in visual acuity at the cortical level but not in the retina. We conclude that the β2 subunit of the nicotinic acetylcholine receptor is necessary for the anatomical and functional development of the visual system.

Emergence of order in visual system development.

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns.

Visual function studies during exposure to a mixture of diabasic esters (DBE) in Long-Evans rats : cooperative research and development agreement with E.I. Du Pont de Nemours & Company.

Mode of access: Internet.

Visual detection of driving while intoxicated. Project interim report: identification of visual cues and development of detection methods.

National Highway Traffic Safety Administration, Washington, D.C.

City appearance and the law : a manual to assist in the development of ordinance-based visual improvement programs in smaller cities /

Includes bibliography.

Development of a near activity visual questionnaire to assess accommodating intraocular lenses

Purpose: To develop a questionnaire that subjectively assesses near visual function in patients with 'accommodating' intraocular lenses (IOLs). Methods: A literature search of existing vision-related quality-of-life instruments identified all questions relating to near visual tasks. Questions were combined if repeated in multiple instruments. Further relevant questions were added and item interpretation confirmed through multidisciplinary consultation and focus groups. A preliminary 19-item questionnaire was presented to 22 subjects at their 4-week visit post first eye phacoemulsification with 'accommodative' IOL implantation, and again 6 and 12 weeks post-operatively. Rasch Analysis, Frequency of Endorsement, and tests of normality (skew and kurtosis) were used to reduce the instrument. Cronbach's alpha and test-retest reliability (intraclass correlation coefficient, ICC) were determined for the final questionnaire. Construct validity was obtained by Pearson's product moment correlation (PPMC) of questionnaire scores to reading acuity (RA) and to Critical Print Size (CPS) reading speed. Criterion validity was obtained by receiver operating characteristic (ROC) curve analysis and dimensionality of the questionnaire was assessed by factor analysis. Results: Rasch Analysis eliminated nine items due to poor fit statistics. The final items have good separation (2.55), internal consistency (Cronbach's α = 0.97) and test-retest reliability (ICC = 0.66). PPMC of questionnaire scores with RA was 0.33, and with CPS reading speed was 0.08. Area under the ROC curve was 0.88 and Factor Analysis revealed one principal factor. Conclusion: The pilot data indicates the questionnaire to be internally consistent, reliable and a valid instrument that could be useful for assessing near visual function in patients with 'accommodating' IOLS. The questionnaire will now be expanded to include other types of presbyopic correction. © 2007 British Contact Lens Association.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

The development of calibration and adaptive filtering procedures for neuromagnetic studies of human visual function

This thesis first considers the calibration and signal processing requirements of a neuromagnetometer for the measurement of human visual function. Gradiometer calibration using straight wire grids is examined and optimal grid configurations determined, given realistic constructional tolerances. Simulations show that for gradiometer balance of 1:104 and wire spacing error of 0.25mm the achievable calibration accuracy of gain is 0.3%, of position is 0.3mm and of orientation is 0.6°. Practical results with a 19-channel 2nd-order gradiometer based system exceed this performance. The real-time application of adaptive reference noise cancellation filtering to running-average evoked response data is examined. In the steady state, the filter can be assumed to be driven by a non-stationary step input arising at epoch boundaries. Based on empirical measures of this driving step an optimal progression for the filter time constant is proposed which improves upon fixed time constant filter performance. The incorporation of the time-derivatives of the reference channels was found to improve the performance of the adaptive filtering algorithm by 15-20% for unaveraged data, falling to 5% with averaging. The thesis concludes with a neuromagnetic investigation of evoked cortical responses to chromatic and luminance grating stimuli. The global magnetic field power of evoked responses to the onset of sinusoidal gratings was shown to have distinct chromatic and luminance sensitive components. Analysis of the results, using a single equivalent current dipole model, shows that these components arise from activity within two distinct cortical locations. Co-registration of the resulting current source localisations with MRI shows a chromatically responsive area lying along the midline within the calcarine fissure, possibly extending onto the lingual and cuneal gyri. It is postulated that this area is the human homologue of the primate cortical area V4.

The development of the visual system in pre-term infants as assessed by electrophysiological techniques

In an endeavour to provide further insight into the maturation of the human visual system, the contiguous development of the pattern reversal VEP, flash VEP and flash ERG was studied in a group of neurologically normal pre-term infants, born between 28 and 35 weeks gestation. Maturational changes were observed in all the evoked electrophysiological responses recorded, these were mainly characterised by an increase in the complexity of the waveform and a shortening in the latency of the response. Initially the ERG was seen to consist of a broad b-wave only, with the a-wave emerging at an average age of 40 weeks PMA. The a-wave showed only a slight reduction in latency and a modest increase in amplitude as the infant grows older, whereas the changes seen in the ERG b-wave were much more dramatic. Pattern reversal VEPs were successfully recorded for the first time during the pre-term period. Flash VEPs were also recorded for comparison. The neonatal pattern reversal VEP consistently showed a major positive component (P1) of long latency. As the infant grew older, the latency of the P1 component decreased and was found to be negatively correlated with PMA at recording. The appearance of the N1 and N2 components became more frequent as the infant matured. The majority of infants were found to be myopic at birth and refractive error was correlated with PMA, with emmetropisation occurring at about 45 weeks PMA. The pattern reversal VEP in response to 2o checks was apparently unaffected by refractive error.

Development of visual evoked responses to tritan,red-green and luminance stimuli in human infants

The principal aim of this work was to investigate the development of the S-cone colour-opponent pathway in human infants aged 4 weeks to 6 months. This was achieved by recording transient visual evoked responses to pattern-onset stimuli along a tritanopic confusion axis (tritan stimuli) at and around the adult isoluminant match. For comparison, visual evoked responses to red-green and luminance-modulated stimuli were recorded from the same infants at the same ages. Evoked responses were also recorded from colour-normal adults for comparison with those of the infants. The transient VEP allowed observation of response morphology as luminance differences were introduced to the chromatic stimuli. In this way, an estimate of isoluminance was possible in infants. Estimated isoluminant points for a group of six infants aged 6 to 10 weeks closely approximated the adult isoluminant match. This finding has implications for the use of photometric isoluminance in infant work, and suggests that photopic spectral sensitivity is similar in infants and adults. Abnormalities of the visual evoked responses to tritan, red-green and luminance-modulated stimuli in an infant with cystic fibrosis are reported. The results suggest abnormal function of the retino-striate visual pathway in this infant, and it is argued that these may be secondary to his illness, although data from more infants with cystic fibrosis are needed to clarify this further. A group of nine healthy infants demonstrated evoked responses to tritan stimuli by 4 to 10 weeks and to red-green stimuli by 6 to 11 weeks post-term age. Responses to luminance-modulated stimuli were present in all nine infants at the earliest age tested, namely 4 weeks post-term. The slightly earlier age of onset of evoked responses to tritan stimuli than for red-green may be explained by the relatively lower cone contrast afforded by red-green stimuli. Latency of the evoked response to both types of chromatic stimuli and to luminance-modulated stimuli decreased with age at a similar rate, suggesting that the visual pathways transmitting luminance and chromatic information mature at similar rates in young infants.

Prenatal augmented auditory stimulation and visual system development: Effects of timing on intersensory organization

This study investigated the effects of augmented prenatal auditory stimulation on postnatal visual responsivity and neural organization in bobwhite quail (Colinus virginianus). I delivered conspecific embryonic vocalizations before, during, or after the development of a multisensory, midbrain audiovisual area, the optic tectum. Postnatal simultaneous choice tests revealed that hatchlings receiving augmented auditory stimulation during optic tectum development as embryos failed to show species-typical visual preferences for a conspecific maternal hen 72 hours after hatching. Auditory simultaneous choice tests showed no hatchlings had deficits in auditory function in any of the groups, indicating deficits were specific to visual function. ZENK protein expression confirmed differences in the amount of neural plasticity in multiple neuroanatomical regions of birds receiving stimulation during optic tecturn development, compared to unmanipulated birds. The results of these experiments support the notion that the timing of augmented prenatal auditory stimulation relative to optic tectum development can impact postnatal perceptual organization in an enduring way.^